Presentation Title

cell-derived XCL1 induces protective immune responses against West Nile virus within the CNS

Faculty Mentor

Dr. Douglas Durrant

Start Date

23-11-2019 10:45 AM

End Date

23-11-2019 11:30 AM

Location

58

Session

poster 4

Type of Presentation

Poster

Subject Area

biological_agricultural_sciences

Abstract

West Nile Virus (WNV) is a leading cause of mosquito-borne neuroinvasive disease in the US. Following infection, neurological disease can range from febrile illness to lethal encephalitis, yet to date there remains no vaccine or specific treatments for WNV. Previous studies have shown that the proper activation of virus-specific T cells results in protection from WNV infection and any associated neurological disease. Dendritic cells (DCs) are often defined as pivotal inducers of immunity due to their role in activating immune defense mechanisms against invading pathogens within T cells. XCR1 is a chemokine receptor expressed exclusively by a subset of DCs. In fact, XCR1+ DCs have been shown to be essential in cross-presenting antigen and in activating anti-viral immunity. However, DCs are not readily present within the CNS and it remains unknown how DCs are recruited to the CNS during WNV encephalitis to fully activate antiviral immunity. XCL1, the ligand for XCR1, is expressed by activated T cells, DCs, macrophages, and NK cells. We hypothesize that following WNV infection, virus-specific T cells within the CNS produce XCL1 in order to recruit and stabilize their interaction with XCR1+ DCs thus ensuring their proper activation and subsequent protection against WNV encephalitis. Here we demonstrate that mice lacking XCR1+ DCs were more susceptible to WNV encephalitis, displayed increased neuronal cell death, as well as increased viral burden compared to control animals suggesting the XCR1+ DCs are crucial in antiviral protection. In addition, we found that in the absence of XCL1 signaling, WNV-infected animals displayed increased parenchymal localization of T cells within the brain compared to controls. These data indicate that XCL1-XCR1 interactions are crucial in the development of efficient anti-viral immunity. The knowledge gained from this work may then be applicable to other viral diseases of the CNS and more.

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Nov 23rd, 10:45 AM Nov 23rd, 11:30 AM

cell-derived XCL1 induces protective immune responses against West Nile virus within the CNS

58

West Nile Virus (WNV) is a leading cause of mosquito-borne neuroinvasive disease in the US. Following infection, neurological disease can range from febrile illness to lethal encephalitis, yet to date there remains no vaccine or specific treatments for WNV. Previous studies have shown that the proper activation of virus-specific T cells results in protection from WNV infection and any associated neurological disease. Dendritic cells (DCs) are often defined as pivotal inducers of immunity due to their role in activating immune defense mechanisms against invading pathogens within T cells. XCR1 is a chemokine receptor expressed exclusively by a subset of DCs. In fact, XCR1+ DCs have been shown to be essential in cross-presenting antigen and in activating anti-viral immunity. However, DCs are not readily present within the CNS and it remains unknown how DCs are recruited to the CNS during WNV encephalitis to fully activate antiviral immunity. XCL1, the ligand for XCR1, is expressed by activated T cells, DCs, macrophages, and NK cells. We hypothesize that following WNV infection, virus-specific T cells within the CNS produce XCL1 in order to recruit and stabilize their interaction with XCR1+ DCs thus ensuring their proper activation and subsequent protection against WNV encephalitis. Here we demonstrate that mice lacking XCR1+ DCs were more susceptible to WNV encephalitis, displayed increased neuronal cell death, as well as increased viral burden compared to control animals suggesting the XCR1+ DCs are crucial in antiviral protection. In addition, we found that in the absence of XCL1 signaling, WNV-infected animals displayed increased parenchymal localization of T cells within the brain compared to controls. These data indicate that XCL1-XCR1 interactions are crucial in the development of efficient anti-viral immunity. The knowledge gained from this work may then be applicable to other viral diseases of the CNS and more.